Lactone production



saturated-'y-lactone.

United States Patent 3,177,227 LACTONE PRODUCTION George B. Payne, Berkeley, Calif, assignor to Shell Gil Company, New York, N.Y., a corporation of Delaware No Drawing. Filed Jan. 30, 1963, Ser. No. 255,080 7 Claims. (Cl. 260-3436) This invention relates to an improved process for the production of lactones. More specifically, it relates to a process for the production of alpha, beta-ethylenically unsaturated-'y-lactones.

The general class of unsaturated lactones is old in the art, being described, for example, by Haynes and Jones, J. Chem. Soc., 954 (1946), who prepared unsaturated- 'y-lactones by partial hydrogenation of products resulting from condensation of ketones and acetylene. Such materials were found to inhibit the growth of certain plants and seeds, i.e. cress seeds. These unsaturated lactones have also been found to be suitable monomers for the production of superior polymersand copolymers.

It is therefore an object of this invention to provide a process for the production of unsaturated lactones. More specifically, it is an object of the invention to provide a process for the production of alpha,beta-ethylenically unsaturated-'y-lactones. A further object is to provide a process for the epoxidation of betagy-olefinically unsaturated carboxylic acids, the product of which may be readily converted to alpha,beta-ethylenically unsaturated-'y-lactones.

These objects are achieved by the novel process which comprises the epoxidation of a beta,'y-olefinically unsaturated acid to form the corresponding betaq-epoxyacid, conversion of the epoxyacid to the corresponding beta-hydroxy-y-lactone, and dehydration of the betahydroxy- -lactone to the alpha,beta-ethylenically un- As will be disclosed hereinafter, such steps may be performed individually or in a more or less continuous manner, and both such processes are within the contemplated scope of the invention.

The starting materials of the process are carboxylic acids possessing beta,'y-ethylenic unsaturation. The preferred class of acids of this type are those 3-alkenoic acids represented by the formula R/ I l. R

wherfin R is hydrogen, alkyl or aryl including aralkyl and alkaryl, and especially the lower betagy-alkenoic acids.

Preferred R groups are hydrogen, alkyl having from 1 to 10 carbon atoms and aryl having up to 10 carbon atoms. Illustrative of preferred alkyl R groups are methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, tertbutyl and the isomeric pentyl, hexyl, heptyl, octyl, nonyl and decyl radicals. Preferred aromatic R groups include 'phenyl, benzyl, tolyl, xylyl, alpha-phenylethyl and naph- 3,177,227 Patented Apr. 6, 1965 epoxidized to an intermediate corresponding 3,4-epoxyalkanoic acid, which may react further under the conditions of the epoxidation. The epoxidation may be effected by the use of a number of organic or inorganic oxidizing agents.

Because of the high yields obtained by the use thereof, and the relative ease of effecting reaction, the preferred epoxidizing agents are the peracids, including inorganic and organic peracids. Illustrative of suitable inorganic peracids are peracids formed from metallo-acids or metallo-acidic oxides, particularly those containing metals of Groups V-VI of the periodic table, e.g. pertungstic acid, pervanadic acid, perchromic acid and permolybdic acid. Pertungstic acid is the preferred epoxidizing agent of this class. Exemplary organic peracids include the aliphatic monocarboxylic peracids such as performic acid, peracetic acid, perpropionic acid and perpivalic acid; the aromatic peracids such as perbenzoic acid, and monoand di-perphthalic acid, and peroxycarboximidic acids formed, for example by the reaction of hydrogen peroxide and a nitrile, e.g. acetonitrile and benzonitrile. Preferred organic peracids have from 1 to 6 carbon atoms.

The epoxidation may be conducted by any of several preferred methods. Using a preformed peracid, the alkenoic acid to be epoxidized and the peracid are reacted in liquid phase solution by dissolving both in a suitable solvent, or by dissolving one reactant in such a solvent and adding the other reactant in increments, either as a free substance or in solution in the same or some other miscible solvent. Using this procedure, at least a stoichiometric amount of peracid is required, that is, at least one mole of peracid is used for each mole of unsaturated acid. Preferably, the peracid is employed in excess, and although molar excesses of peracid up to 50% or more may be used, molar excesses of peracid from about 5% to about 20% are satisfactory.

Alternatively, the peracid may be prepared in situ by reaction of a peracid precursor and hydrogen peroxide, and an in situ preparation of the peracid is the most preferred modification of the epoxidation process. By peracid precursor it is meant a material, e.g. an acid or acidic oxide, that reacts with hydrogen peroxide to form a peracid. These precursors include acids, such as acetic acid, formic acid, phthalic acid or tungstic acid; salts of these acids, e.g. sodium acetate and sodium tungstate, which are converted to the free acid under the acidic conditions of the epoxidation process; and metallo-acidic oxides such as molybdic oxide. One modification of this method comprises mixing the unsaturated acid and the peracid precursor in solution and adding the hydrogen peroxide inincrernents to the mixture. Equivalently useful, however, is the modification wherein the entire amount of hydrogen peroxide is present at the start of reaction. In an in situ preparation of peracid, an equivalent amount of peracid precursor is not required, as peracid is regenerated by additional reaction with hydrogen peroxide. A molar amount of peracid percursor of from about 1% to about 30% based upon the unsaturated acid is usually satisfactory, although a molar amount of from 5% to about 20% on the same basis is preferred. The hydrogen peroxide is employed in molar excess of the unsaturated acid. While molar excesses of up to 50% are operable, a molar excess of hydrogen peroxide from about 5% to about 20% will usually suffice. The hydrogen peroxide may-be employed in any convenient form. Particularly useful are the commercially available aqueous solutions of from 30% to concentration.

Either method of epoxidation is performed in liquid phase solution. Suitable solvents for the epoxidation are those solvents inert to the reaction conditions and liquid at the reaction temperature. Such solvents include the cation of heat.

v.5 I mono.- and polyhydricalcohols, illustrated by methanol,

ethanol, isopropanol, tert-butanol, ethylene glycol, and.

trimethylene glycol; ethers including diethyl ether, dibutyl ether, ethyl hexyl ether, anisole, tetrahydrofuran, tetrahydropyran and lower alkyl ethers of ethylene glycol, diethylene glycol and tetraethylene glycol wherein the alkyl groups have from 1 to 4 carbon atoms; hydroxyethers such as the cellosolves and the carbitols; esters such as ethyl acetate, propyl acetate, methyl butanoate and the like; ketones'such as acetone, methyl isobutyl ketone and acetophenone; hydrocarbons including hexane, isooctane, benzene and toluene; and halogenated hydrocarbons such as carbon tetrachloride,carbon tetrabromide, chloroform, methylene chloride and 1,1,2-trichloro ethane;and mixtures of one or more solvents. An addi-' tional solvent is, of course, water, which is most frequently encountered when aqueous solutions of hydrogen peroxide are employed; In cases where water is present, it is, preferred that other solvent be present in order to give increased solubility to the acid being epoxidized. Co-solvents that are satisfactory in conjunction withwater are those miscible withwater, eg. the lower alcohols and some ethers such as tetrahydrofuran.-

The temperature at which the epoxidation is most efliciently conducted is dependent in part upon whether organic or-inorganic peracids are employed. Using inorganic peracids, temperatures from about to about 100 C. are suitable, although a preferred temperature range is from room temperature, i.e. 2030 C., to about 70 C. Whenv organic peracids are employed, useful temperatures are those from about 0 C. to the reflux temperature of the solution. Preferable temperatures are from about to about 150, with the 10 to 40 C. range most preferred.

The epoxidation is preferably conducted under acidic conditions. Normally, the acid or acids employed as reactantswill give the reaction solution a pH below 7, and under some conditionsit is advantageous to add an amount of basic material to raise the pH to a more desirable level. the'alkali and alkaline earth hydroxides, e.g. sodium hydroxide, potassium hydroxide, cesium hydroxide and barium hydroxide; the corresponding oxides such as barium oxide, sodium oxide and potassium oxide; the alkali metal alkoxides such as sodium methoxide, potassium ethoxide, potassium tert-butoxide and cesiumn-propoxide; salts of strong bases and weak acids including sodium acetate, potassium bicarbonate, sodiumcitrate and the like; and organic bases including the amines, e.g. triethyl amine and pyridine. I

The type of product produced will in part be dependent on the pH of the epoxidation solution and the preferred pH range ,willjvary accordingly. At a pH from about 4 to about 6.5, the principal product is generally epoxyalkanoic acid produced by epoxidation of the betap -ethyleniclinkage of the unsaturated acid reactant. Ata pH below 4, although lower yields of epoxyacid are obtained, the principalbyproduct is the correspondingbeta-hydroxyr'y-lactone, a succeeding intermediate in the desired overall process. Thus, the somewhat lower yield of initial product is compensated by the relative ease of subsequent operation.v The product of epoxidation, therefore,

normally consists of a mixture of the 3,4-epoxyalkanoic acid, and the corresponding beta-hydroxy-y-lactone.

It is possible to separate the mixture into pure components as by fractionation subsequent to removal of solvent andunreacted starting material, but it is equivalently useful tomake no attemptto separate the components, but to ,subject the bottoms product following solvent removal to further operations to promote more extensive lactone formation.

The conversion of epoxy acid to lactone' occurs on standing, although lactonization is promoted by the appli- In fact, some lactonization will occur during slow fractionation of the epoxidation residue.

Suitable basic materials for this purpose include The mixtureof epoxyacid and lactone is converted to lac tone at temperatures from room temperature, i.e. 20-30 C., up to the reflux temperature of-the mixture, although temperatures from about 30 to about C. are to be preferred for formation of beta-hydroxy-y-lactone.

Alternatively, the 3,4-epoxyalkanoic acid or mixture of the beta-hydroxy-y-lactone therewith may be dissolved in a suitable solvent and heated in the presence of a catalytic amount of acid. Suitable solvents include the hydrocarbons, e.g. benzene, toluene, xylene, hexane, isooctane, decane and the like; halogenated hydrocarbons such as carbon tetrachloride, chloroform, carbon tetrabromide, perchloroethane and methylene chloride; and ethers such as dibutyl ether, anisole, tetrahydrofuran, tet-rahydro pyran and dioxane. Acid catalysts for lactone formation include mineral acid, e.g. sulfuric acid, phosphoric acid and hydrogen chloride; sulfonic acids such as methanesulfonic acid and p-toluenesulfonic acid; and various acidic ion exchange resins. When lactonization is effected in solution, temperatures from about 40C; to the reflux temperature of the solution are preferred with the most advantageous temperature-being that of reflux. 1

In either of these procedures, -,1actone'.formation occurs in high yields. The actual product composition will depend, however, on the reaction conditions whereby lactone is formed. Particularly during thermal lactonization dehydration of the beta-hydroxy- -lactone to alpha,betaethylenically unsaturated-y-lactone occurs. This dehy dration is of no disadvantage, however, as the'unsaturated lactone is the desired final product. Thus, should a thermal lactonization process be employed, it is convenient to heat the hydroxylactone to a more elevated temperature,

or to maintain the reaction temperature for a longer period of time to effect cyclization andfldehydration in a continuous operation. It is principally for this reason that thermal lactonization and dehydration procedures are to be preferred.

The dehydration of beta-hydroxy- 'y-lactone mayv also be conducted by means of conventional dehydration techniques. These techniques include heating the hydroxylactone with acidicanhydrides such as phosphorus pentoxide; orsilica gel; refluxing the hydroxylactone in an alcoholic solution of mineral acid, e.g., sulfuric acid or polyphosphoric acid; or refluxing the hydroxylactone with wherein has the previously stated significance.

Exemplary lactones include N -butenolide; a-methylthe like.

As previously stated, these ,alpha,beta ethylenically unsaturated-*y-lactones have found biological utility in the field of growth suppressants. They are also useful as monomers from which polymers may be prepared. The

-five-membered ring is sufiiciently stable toallow polymerization through the ethylenic linkage without attendant ring opening. Thus, homopolymers containing lactone moieties may be prepared or alternatively the'unsaturated lactones may be copolymerizedwith other olefin mono- ;rners. Under suitable conditions, such polymers are crossr." a linked via intermolecular esterification to form polymeric materials of great strength. Alternate polymerization involving ring opening produces polyesters containing reactive olefinic linkages upon which other monomers can be grafted.

To illustrate the novel process of the invention, the following examples are given. It should be understood that these examples are merely illustrative and are not to be regarded as limitations, for the teachings thereof may be varied as will be understood by one skilled in this art.

Example I To a flask equipped with stirrer, thermometer, condenser and pH electrodes were charged 64 g. (0.50 mole) of 2-methyl-3-hexenoic acid, 300 ml. of methanol, 100 ml. of water, 4.0 g. (0.1 mole) of sodium hydroxide, 16.5 g. (0.05 mole) of sodium tungstate dihydrate and 66.7 g. (0.6 mole) of 30% hydrogen peroxide. The mixture was maintained at 60 C. for 2 hours while gently stirred. The meter pH remained steady at 5.2-5.3 throughout the first hour; later it rose to 5.9-6.0. The mixture was cooled to 20 C. and acidified by dropwise addition of sulfuric acid. It was then diluted with 150 ml. of water and extracted with five 100 ml. portions of chloroform. The combined extract was washed with water, dried over magnesium sulfate, and concentrated to a volume of 100 ml. on the steam bath. There was obtained 61 g. of product, shown by analysis to be 68% w. 2-methyl-4-ethyl-3-hydroxybutyrolactone, 20% W. 2- methyl-3,4-epoxyhexanoic acid, and 12% starting material. The yield of C H O products was 84% based upon an 89% conversion of unsaturated acid.

Example II The procedureof Example I was followed, except that 0.50 mole of 3-hexenoic acid was used in place of 2- methyl-hexenoic acid. Again the reaction was complete in two hours. The crude mixture was stripped at below 40 C. by means of a circulating evaporator to a volume of 200 ml. This residue was cooled, treated drop-wise with 0.1 equivalent of sulfuric acid saturated with ammonium sulfate, and extracted with three 100 ml. portions of chloroform. The combined extracts were washed with saturated ammonium sulfate solution and concentrated to low volume under vacuum at less than 40 C.

Analysis of the product indicated it to be a mixture containing about 50% 4-ethyl-3-hydroxybutyrolaotone, 40% of 3,4-epoxyhexanoic acid, and starting material.

Example III A cold solution of 57 g. (0.50 mole) of 3-hexenoic acid in 500 ml. of chloroform was treated with 0.55 mole of peracetic acid and allowed to stand overnight at below 10 C. The mixture was then allowed to stand 24 hours at room temperature. The excess epoxidizing agent was decomposed by 5% palladium on charcoal catalyst; the catalyst was filtered and the mixture concentrated at the water pump using a bath temperature of 40 maximum. The residue was then stabilized at room temperature by pumping overnight at 1-2 mm. The weight of epoxy acid was 62.5 g. By acidity value (0.715 eq./100 g.) and epoxide value (0.675 eq./ 100 g.) the material was found to be 88% pure. The yield based on the amount of peracid utilized was 94%.

Example IV When vinylacetic acid is epoxidized by formic acid and hydrogen peroxide according to a procedure similar to Example 111, good yields of 3,4-epoxybutyric acid are obtained.

Example V The crude epoxy acid prepared by Example III was placed in a flask equipped with a condenser and heated on the steam bath. An exothermic reaction occurred,

causing the flask temperature to rise to about l30-140 C. After about 0.5 hr., the mixture was cooled, diluted with chloroform, dried over magnesium sulfate, concentrated and finally Claisen-distilled. There was obtained 35 g. of product, calculated to be a 64% yield of 3-hydroxy-4-hexanolactone based upon the epoxide content of the starting material. There was also obtained an 11% yield of 'y-ethyl-A -butenolide.

Example VI A solution of 50 g. of 3,4 -epoxyhexanoicacid in ml. of benzene was allowed to reflux overnight on the steam bath. Titration indicated the lactonization to be Example VII To a solution of 25.6 g. (0.20 mole) of 2-methyl-3- hexenoic acid in 200 m1. of chloroform was added 0.22 mole of peracetic acid previously treated with sodium acetate to remove sulfuric acid. The mixture was stirred at 25:1 C. for 18 hours, at which time 88% of the theoretical peracid had been consumed. After an overnight stand with palladium on carbon catalyst to decompose the excess peroxide, the mixture was filtered and concentrated under vacuum at temperatures below 50 C. The concentrate was stabilized at 50 C. and l-2 mm. for 0.5 hr. to give 27 g. of crude epoxyacid which was 91% pure by epoxide value. The yield of this product amounted to 96% based on peracetic acid consumed.

Example VIII When 4-phenyl-3-hydroxybutyrolactone is heated in the presence of polyphosphoric acid, a good yield of y-phenyl- A butenolide is obtained.

Example IX When 3,4-din1ethy-l-3,4-epoxyheptanoic acid is heated in chloroform in the presence of p-toluene sulfonic acid, a good yield of 3,5-dimethyl-3-hydroxy-4-heptanolactone is obtained.

I claim as my invention:

1. The process for the production of a,B-ethylenically unsaturated-'y-lactone which comprises reacting hydrocarbon et-hydro-fl,'y-alkenoic acid represented by the formula H C=C-(JCO;H R I a R wherein R is independently selected from the group consisting of hydrogen, alkyl of from 1 to 10 carbon atoms and aryl of up to 10 carbon atoms with peracid in acidic liquid-phase solution in inert solvent at a temperature from 0 C. to C., heating the resulting product mixture at a temperature above about 30 C., and recovering said a,,8-ethylenically unsaturated-'y-lactone therefrom.

2. The process of claim 1 wherein the peracid is pertungstic acid.

3. The process of claim 1 wherein the peracid is organic monocarboxylic peracid having from 1 to 6 carbon atoms. 4. The process for the production of a,B-ethylenically unsaturated-' -lactone which comprises reacting hydrocarbon a-hydro-B,'y-alkenoic acid represented by the formula wherein R is independently selected from the group con-- sisting of hydrogen, alkyl of from 1 to 10 carbon atoms and aryl of up to 10 carbon atoms with organic monocarboXylic ,peracid having from 1 to 6 carbon atoms in acidic liquid-phase solution in inert solvent at a temperature from 0 C. to 150 C., heating the resulting product mixture at a temperature above about 40 C. in the presence of a catalytic amount of a strong acid, and recovering said 0:,[3 ethylenically unsaturatedw-lactone therefrom. 1

5. The process of claim 4 wherein the peracid is peracetic acid. a

6. The process for the production of A -butenolide by reacting 3-butenoic acid with peracid in acidic liquidphase solution in inert solvent at a temperature from 0 C. to 150 C., heating the resulting product mixture at a temperature above about 40 C. in the presence of a catalytic amount of a strong acid, and recovering A butenolide therefrom.

7. The process of claim 6 wherein. the peracidis performic acid.

References Cited by-the-Examiner V UNITED STATESPATENTS 2,356,153 8/44 Elderfield et al. .260-343.6 2,359,208 9/44 Elderfield .et 260-34356 2,361,967 11/44 Ruzicka 260343.6

OTHER, REFERENCES WALTER A. -MODANCE,' Primary Examiner.

N. s. RIZZO, Examiner. 

1. THE PROCESS FOR THE PRODUCTION OF A,B-ETHYLENICALLY UNSATURATAED-$-LACTONE WHICH COMPRISES REACTING HYDROCARBON A-HYDRO-B,$-ALKENOIC ACID REPRESENTED BY THE FORMULA 